tbuckley/cabot-search huggingface dataset:
Abstract 12840: The Risk of Hemorrhagic Stroke Among Various Statins Carrying Intensive LDL-Lowering Capability in Asians
Authors: Po-Sheng Chen, Jia-Ling Lin, Hui-Wen Lin, Sheng-Hsiang Lin, Yi-Heng Li
Journal: Circulation (2022)

Background: Although high-intensity statin (HIS) is recommended in modern lipid guidelines, hemorrhagic stroke (HS) is one of the concerns in Asia because HIS was reported to increase the risk of intracerebral hemorrhage. Whether the HS risk is different among different high potency statins was unknown. Methods and Results: We screened the database of the Taiwan National Health Insurance from January 2013 to December 2018. Adults (≥ 18 years old) who received pitavastatin 2-4 mg/d plus ezetimibe 10 mg/d (combination group) and those who received atorvastatin 40 mg/day or rosuvastatin 20 mg/day (HIS group) for any reason were enrolled for further analysis. The primary endpoint was HS. We also assessed the differences of a composite safety outcome which included hospitalization for drug-related hepatitis or myopathy and new onset diabetes. All censored subjects were follow-up till December 2019. After 1:10 propensity matching, 41437 patients were included (37670 with HIS and 3767 with combination group). After median follow-up for 3.05 ± 1.66 years, HS occurred in 1.29% and multivariable analysis showed subjects in combination group had lower rate of HS than those in HIS group (combination vs. HIS, adjusted HR: 0.650, 95% CI: 0.443-0.953). Moreover, pre-specified subgroup analysis showed similar results in those with previous history of HS or ischemic stroke as whole population. In composite safety endpoint, there was no difference between these two groups (combination vs HIS, adjusted HR: 0.910, 95% CI: 0.809-0.953). Conclusions: Our study showed Asian general population with pitavastatin plus ezetimibe had less HS during follow-up comparing to those having HIS. These results suggested that pitavastatin plus ezetimibe was a favorable choice in Asian population who needed strict lipid control but with concern of HS.
Abstract 11483: Rationale and Design of Randomized Controlled Trial Evaluating an Atrial Appendage Micrograft Transplantation in Conjunction With Coronary Artery Bypass Surgery
Authors: Vilbert T Sikorski, Annu Nummi, Severi Mulari, Esko M Kankuri, Antti E Vento
Journal: Circulation (2022)

Introduction: In addition to the revascularization therapies for ischemic heart disease (IHD), such as coronary artery bypass grafting (CABG), tissue-engineered cell therapies can help further improve myocardial repair. First clinical results on autologous right atrial appendage-derived micrograft (AAM) transplantation have demonstrated excellent safety and feasibility profiles and suggested a therapeutic effect on myocardial viability. This randomized clinical trial aims to extend the evaluation of efficacy of AAMs transplantation when combined with CABG surgery. Methods and objectives: This double-blinded randomized controlled AAMS2 trial will assess the benefits, safety, and feasibility of the perioperatively assembled and epicardially transplanted AAMs-patch in conjunction with CABG. The trial recruits a total of 50 patients, half of which are randomized to receive the AAMs-patch (CABG+AAMs) and the other half to undergo a standard CABG. Prior to surgery, cardiac structure and function are assessed with late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMRI), electrocardiogram, and transthoracic echocardiography (TTE). LGE-CMRI, electrocardiogram, and TTE are repeated at 6-month follow-up for structural and functional comparisons to baseline. The primary endpoints focus on the efficacy of the AAMs patch as evaluated by LGE-CMRI and TTE as well as changes in health-related quality of life assessments, 6-minute walk test or N-terminal-pro-BNP levels. The secondary endpoints centre on feasibility and safety. For molecular and especially RNA-level analysis of the response to therapy in blood, RNA-stabilized whole blood and plasma samples are collected. Conclusions: The AAMS2 trial is expected to provide further feasibility and safety data as well as insights for efficacy of epicardial AAMs-patch transplantation when administered during CABG surgery.
Abstract 12818: Microrna Biomarkers Target Genes and Pathways Associated With Type 2 Diabetes
Authors: Dorian Kariuki, Bradley E Aouizerat, Kesava Asam, Alka M Kanaya, Jose Florez, Li Zhang, Elena Flowers
Journal: Circulation (2022)

Introduction: Type 2 diabetes (T2D) is a major risk factor for cardiovascular disease (CVD), and CVD remains a leading cause of death among those living with T2D. MicroRNAs (miRs) target messenger RNAs (mRNAs) to alter gene expression, and circulating miRs, which are readily measured from blood, have been studied as potential biomarkers for T2D risk. Our prior analysis of the Diabetes Prevention Program identified a subset of five miRs that were optimal predictors of incident T2D with interactions by trial arm. The purpose of this study was to identify the mRNA and biological pathways targeted by these five miRs to elucidate potential mechanisms of risk and responses to the tested interventions. Methods: We obtained experimentally validated human data from miRTarBase (version 8.0), filtered and subsetted the data using R (version 4.1.1) to identify mRNAs with strong evidence of being regulated by the five miRs. Pathway analysis was employed to assess for overrepresentation of the mRNA targets of miRs using the Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation database and clusterProfiler (version 4.2.2) package. Results: The five miRs targeted a total of 167 pathways and 122 genes. Among the identified pathways, nine have known T2D associations: Insulin signaling, Insulin resistance, Diabetic cardiomyopathy, T2D, AGE-RAGE signaling in diabetic complications, HIF-1 signaling, TGF-beta signaling, Fatty acid biosynthesis, and Endocrine resistance. Of these, AGE-RAGE signaling was targeted by all five miRs and HIF-1 signaling was targeted by all except miR-144. A total of 36 genes were targeted in the two pathways. Vascular endothelial growth factor A (VEGFA) was targeted by miR-186, miR-203a, miR-205, and miR-206 in both AGE-RAGE and HIF-1 signaling pathways. Among genes that were targeted by two or more miRs, BCL2 apoptosis regulator (BCL2) and VEGFA have prior genetic associations with risk for T2D. Conclusions: These findings suggest that miR predictors of incident T2D target mRNAs and pathways known to underlie risk for T2D. Future studies can evaluate miRs as potential therapeutic targets for preventing and treating T2D and for informing mechanisms underlying risk reduction interventions, allowing for more precise treatments for individuals.
Abstract 14328: The Impact of Peripheral Arterial Disease in Major Bleeding and Major Cardiac and Cerebrovascular Events in Patient Undergoing Percutaneous Coronary Intervention: A Contemporary Assessment
Authors: Md R Bhuiyan, Tia Bimal, Joanna Fishbein, Samy Selim, Puneet Gandotra, Lawrence Ong, Luis Gruberg
Journal: Circulation (2022)

Introduction: Peripheral arterial disease (PAD) has been associated with adverse outcomes in patients undergoing percutaneous coronary intervention (PCI). However, there are controversial reports regarding its impact in the current era of radial interventions. Hypothesis: We assessed the hypothesis that patients with PAD and patients without PAD undergoing PCI have similar major bleeding complications and major adverse cardiac and cerebrovascular events (MACCE). Methods: This was a retrospective analysis of data collected from 6 New York metropolitan area tertiary care hospitals and submitted to the NCDR between 2010 and 2018. Major bleeding events were classified using Bleeding Academic Research Consortium (BARC) classification. Severe bleeding was defined as a BARC ≥3. Hierarchical logistic regression was utilized to assess the association of PAD with post-PCI adverse outcomes, as appropriate. Results: A total of 2,933 PAD patients (9.4%) underwent PCI (without PAD, n = 28,172). Results are shown in the Table. PAD patients had a significantly higher odds of MACCE and major bleeding complications, including blood transfusions and in-hospital mortality. Access site bleeding and the need for post PCI dialysis did not reach statistical significance. A multivariable analysis will be presented. Conclusions: In conclusion, PAD continues to be a major risk factor for patients undergoing PCI. When compared with patients without PAD, these patients are at an increased risk of major adverse outcomes, including a 67% increase in mortality risk and a 44% in major bleeding complications risk.
Abstract 13976: Trends in Cardiovascular Health Status During Early vs Late Adolescence, 2007-2018
Authors: Carissa M Baker-Smith, Tiffany M Powell-Wiley, Loni P Tabb, Bonita E Falkner, Robert E Akins
Journal: Circulation (2022)

Introduction: Identification of factors associated with preservation of cardiovascular health (CVH) during adolescence may inform strategies to reduce CV disease burden in adulthood. Hypothesis: CVH status is worse in later (16-18 years) vs early (13-15 years) adolescence and is influenced by socioeconomic factors. Methods: National Health and Nutrition Examination Survey (NHANES) 2007 to 2018 data (6 most recent complete survey cycles) analyzed. CVH status was characterized by AHA Life Simple 7 score (AHAS7). A representative sample (N=5874) of the US adolescent population was analyzed and weights used to estimate trends for the entire US adolescent population. The proportion of US adolescents with ideal (AHAS7 score 12-14), intermediate (8-11), and poor (0-7) CVH status calculated. Consecutive 2-year NHANES cycles were rescaled to consecutive integers to assess change in CVH score over time. Regression models were used to assess trend in CVH score over time and separately by age. Nonlinearity of secular trend was tested by assessing the significance of adding a quadratic term to the regression model (significance, p&lt;0.01). CVH status by early vs late adolescence was assessed via categorical analysis as was the association between CVH status in early vs late adolescence and social determinants such as insurance status, poverty status (above and below 5x’s the national poverty level) and household reference (e.g., parent) education level. Results: CVH scores improved from 2007 to 2018 ( p&lt;0.0001 ), however, the proportion of youth with ideal CVH status declined with age and was highest in early and lowest in later adolescence (early 59% vs later 41%) ( p&lt;0.0001 ). The proportion of adolescents with ideal physical activity, smoking status, blood pressure, and cholesterol was lowest among older adolescents. Older adolescents are more likely to have no insurance (early 44% vs later 56%, p&lt;0.0001 ). Other social determinants were not significantly different. Conclusions: Efforts to improve CVH status should begin no later than adolescence. Greater focus on preserved physical activity, BP and cholesterol management, reduced smoking and maintenance of health insurance coverage may lead to sustained CVH status throughout adolescence.
Abstract 13881: Utility of Cardiac CT for Evaluation of Infectious Endocarditis
Authors: Deeptanshu Jain, Satish Pendela, Tanya Sharma Jain, Nikita Nand, Mohamed Diab, David Corteville
Journal: Circulation (2022)

Background: Infectious endocarditis (IE) usually presents with variable imaging findings and is associated with high morbidity and mortality. Transesophageal echocardiography (TEE) is the gold standard method for diagnosing IE. However, the presence of prosthetic or calcified valves poses a diagnostic challenge for detection of IE and associated structural abnormalities. In recent years, there is growing literature supporting cardiac CT scan as an adjunct to TEE in such cases. Studies have also shown that cardiac CT has significantly high sensitivity for detecting peri-annular complications. Case A 79 year old male who underwent transcatheter aortic valve replacement (TAVR) for severe aortic stenosis one year ago presented with a one week history of worsening confusion and fatigue. His prior medical history includes non-ischemic cardiomyopathy with low ejection fraction (30-35%), deep vein thrombosis (DVT) and pulmonary embolism (PE). Labs were notable for leucocytosis 27,300/uL and thrombocytopenia with platelet count 20,000/uL. Patient was bacteremic with blood cultures growing oxacillin-resistant Staphylococcus epidermidis. TEE revealed a small vegetation concerning for infection versus thrombus. A CT abdomen revealed a 3.8 cm splenic infarct. Tagged WBC scan was thereafter considered to help delineate, but came back negative. Decision Making In setting of thrombocytopenia, repeat TEE was deemed unsafe. Alternatively, the patient underwent cardiac CTA which revealed hypoattenuating leaflet thickening (HALT) involving &gt;75% of aortic valve leaflets (Figure 1) with no perivalvular leak or abscess thereby confirming IE. Conclusion Cardiac CT offers distinct advantages and has emerged as a great adjunct to echocardiography for the workup of IE, especially in patients who have contraindications to TEE or with prosthetic valves where echocardiography is sub-optimal. The report further elucidates the role of cardiac CT as an imaging adjunct for IE.
Abstract 14124: Acute Mitral Regurgitation With Chronic Endocarditis in Type I Osteogenesis Imperfecta
Authors: Riya Sam, Abhinav K Vulisha, Neharika Bhardwaj, Charles Ogdon, Prateeth Pati
Journal: Circulation (2022)

Case Presentation: A 45-year-old man with history of Type I osteogenesis imperfecta (OI) presented with severe shortness of breath and worsening bilateral lower extremity edema for 6 weeks. Paternal family history was significant for Type I OI with early deaths in affected females. Physical examination revealed a distressed man with blue - gray sclerae and jugular venous distention. Cardiopulmonary examination was remarkable for tachycardia, grade IV holosystolic murmur radiating to the axilla, bilateral lung crackles with decreased air entry on the lower lung fields and pitting pedal edema up to mid thighs. TTE and TEE were significant for severe eccentric posterior MR with multiple vegetations versus ruptured chordae and normal systolic function. He underwent an emergency mitral valve replacement complicated by post-operative severe AR requiring redo sternotomy with aortic valve replacement. Histologically, aortic valve leaflets were suggestive of chronic endocarditis with dual negative sets of blood cultures drawn since admission. He was eventually discharged home after an intense cardiac rehabilitation with appropriate follow ups. Discussion: OI is a rare hereditary connective tissue disorder affecting the production of Type I collagen due to mutations in COL1A1 and COL1A2 genes. Although lesser known, OI valvulopathy is typically limited to the left sided structures, for unknown reasons, with the most common valvular anomaly being AR followed by MR. Despite the dramatic cardiac involvement in our patient and known mortality risk associated with surgical intervention, prompt evaluation and early intervention led to a successful outcome.
Abstract 14157: Effects of Follistatin on the Regulation of Vascular Function by Perivascular Adipose Tissue in a Model of Essential Hypertension
Authors: Ann Kuganathan, Marcos Leal, Vincent Lu, Bo Gao, Jeffrey Dickhout, Joan C Krepinsky
Journal: Circulation (2022)

Introduction: We previously showed that follistatin (FST), a potent activin inhibitor, lowers BP in the spontaneously hypertensive rat (SHR), a model of essential HTN. This was associated with improved vessel structure (reduced collagen) and function (reduced hypercontractility and improved endothelium-dependent relaxation). FST also reduced vascular oxidative stress (ROS). Perivascular adipose tissue (PVAT) is known to regulate vascular tone. FST induces browning and thus increased thermogenic activity of peripheral adipose tissue. Transition from white to brown adipose tissue is associated with decreased risk of CVD. Here, we assess FST effects on PVAT and its regulation of SHR vascular function. Methods: SHR were treated with FST from 12-20 weeks of age. Normotensive WKY rats served as controls. Mesenteric resistance arteries were isolated with or without intact PVAT. Vessel function was assessed using wire myography. In separate studies, white mesenteric and brown aortic PVAT, or peripheral fat depots, were isolated from WKY rats. These were introduced to WKY mesenteric vessels to study PVAT-isolated function. Results: Intact PVAT augmented constriction to KCl in SHR, but not WKY arteries, an effect prevented by FST. Improvement in endothelium-dependent vasodilation in FST-treated SHR was PVAT-dependent. SHR PVAT had increased adipocyte size and ROS (by DHE), both reversed by FST. Isolated PVAT from WKY incubated with pyocyanin (30’) to induce ROS augmented the KCl response, suggesting that FST inhibition of PVAT oxidative stress in HTN restores beneficial vascular effects. Incubation of WKY vessels with brown PVAT inhibited constriction to KCl more effectively than did white PVAT. Interestingly, peripheral white adipose (inguinal) did not have any anticontractile effect. Brown adipose (interscapular) effects were intermediate. Conclusions: Improvement in anticontractile effects of PVAT by FST in resistance vessels is associated with reduced PVAT oxidative stress. Brown PVAT is more effective than white PVAT in inhibiting vessel contraction, and unlike white PVAT, peripheral white adipose does not have anticontractile effects. Future work will assess effects of FST on PVAT browning, and whether browning itself can improve BP.
Abstract 13448: Time Course and Predictors of Renal Function Decline After Pediatric Heart Transplantation: A PHTS Multi-Institutional Analysis
Authors: Manu R Varma, Marc E Richmond, Devin A Koehl, Othman A Aljohani, Vernat J Exil, Adam K Morrison, Aryaz Sheybani, Shelby White, Ryan S Cantor, James K Kirklin, Pirooz Eghtesady
Journal: Circulation (2022)

Introduction: Decline in renal function can impact both the management and outcomes of pediatric heart transplantation (HTx). Initial renal function decline may be subclinical and underappreciated. We sought to identify the time course and predictors of decline in renal function and the impact of these changes on HTx outcomes. Methods: The Pediatric Heart Transplant Society (PHTS) database was queried to identify HTx recipients at participating centers from 1996 to 2019 with at least 1 year of follow-up. Patients with simultaneous or previous kidney transplant were excluded. Renal function was measured by modified Schwartz formula eGFR on annual follow-up forms and stratified into eGFR groups by National Kidney Foundation chronic kidney disease staging guidelines. “Initial renal function decline” was defined as the initial drop by at least one eGFR group relative to stage at 1 year post transplant (“baseline”). Results: Of the 5,250 patients who met inclusion criteria, initial renal function decline occurred, relative to baseline, in 7.4%, 18.7%, and 55.7%, by 1, 5, and 10 years of follow up, respectively (Figure A). eGFR group distribution for the cohort progressively worsened over the follow up period (Figure B). On multivariate Cox modeling, risk factors for renal function decline were increased BSA at 1 year post-transplant (HR 1.24 [1.02, 1.52]), acute rejection with hemodynamic compromise (HR 1.24 [1.10, 1.39]), and Black race (HR 1.21 [1.08, 1.36]) with the use of tacrolimus (vs cyclosporine) being protective (HR 0.77 [0.69, 0.85]). Patients whose eGFR was &lt; 30 mL/min at 1 year follow up had an increased risk of graft loss (P &lt; 0.0001 compared to all other groups). Conclusions: Decline in renal function occurs progressively, affecting over 50% of HTx recipients in long term follow up, independent of renal condition at the time of HTx. Avoidance of potentially nephrotoxic events and medications must be considered at all times in the long term management of pediatric HTx.
Abstract 13208: Pathways Linking Posttraumatic Stress Disorder to Ischemic Heart Disease in Women Veterans
Authors: Ramin Ebrahimi, paul dennis, Carlos Alvarez, Aaron Perkins, Hui Yang, Annie L Shroyer, jean beckham, Jennifer Sumner
Journal: Circulation (2022)

Introduction: Posttraumatic stress disorder (PTSD) is associated with increased risk of ischemic heart disease (IHD). It is unclear if this excess risk is entirely mediated through traditional IHD risk factors (hyperlipidemia, hypertension, diabetes, and smoking). We examined 13 potential mediators of the PTSD-IHD association in a large cohort of women veterans: traditional risk factors, other conditions (obesity, chronic kidney disease, neuroendocrine disorders), women-specific risk factors (e.g., gestational diabetes and hypertension, pre-eclampsia), and psychiatric disorders (depression, anxiety, psychotic disorders, alcohol dependence, and drug dependence). Methods: The study cohort included women veterans ≥18 years of age who were enrolled in Veterans Health Administration care between 1/1/2000 to12/31/2017. Diagnosis of each risk factor and disorder was based on administrative billing codes (International Classification of Disease versions 9 and 10). The final study cohorts included 1:2 propensity-score matched group of patients with and without PTSD respectively. The cohorts were matched for age, number of prior visits, and presence of the above risk factors. Cox regression examined associations of PTSD with time to development of the above 13 risk factors. Cox regression with time-varying covariates was used to model time to development of IHD as a function of PTSD and each of above 13 risk factors as time-varying predictors in separate models. Results: The cohorts included 132,293 patients with, and 265,846 patients without PTSD. PTSD was positively associated with each of the 13 risk factors. Results are tabulated in the table below.Conclusion: Traditional risk factors cumulatively accounted for just one third of the risk of IHD posed by PTSD, and all examined risk factors accounted for less than half of the increased risk associated with PTSD. More research is needed to identify pathways by which PTSD accelerates cardiovascular risk.